This project will continue our experimentation to establish the mechanisms involved in the heterogeneity expressed within the mononuclear phagocyte (MO) system. This is necessary in order to develop optimum procedures for immunotherapy against cancer and virus infections by intervention in the MO system. We will pursue four distinct, but complementary, approaches. i) Separate peritoneal MO into subsets and define their developmental interrelationships invivo and in vitro. Each subset will be characterized by morphological, ectoenzyme and immunological criteria, and for antiviral and antitumor functions. (ii) Delineate the developmental proceses in MO proliferating from peritoneal and bone marrow precursors, by establishing the proliferative capacity of the MO subsets and the sequential changes in the various criteria and functions. (iii) Define the induction, regulation and expression processes in MO activation in beige mice (Chediak-Higashi syndrome) and 89Sr-treated mice (bone marrow-ectomied). These models provide unique opportunities to define the activation process in mice deficient in circulating monocytes (89Sr), and to define the development and roles of MO and NK cells (deficient in both mice) against tumors and viruses. (iv) Establish the developmental relationships in human MO-like cell lines during differentiation/maturation in regard to antiviral resistance.